By Susannah Baruch

from GeneWatch 27-1 | Jan-Apr 2014

Reproduction is not genetically simple. For every set of biological parents, trillions of possible genetic combinations are possible in each offspring. We live in an era of dramatically increasing knowledge about the human genome. The possibility of a "$1,000 genome" - full genetic sequencing for any individual who seeks it - is held out as a possibility in the near future.

How does our heightened expectation to know more about our genetic makeup affect third party reproduction, where a gamete donor - an egg or sperm donor - accounts for half of a child's genetic makeup?

Since long before this age of genomics, prospective egg and sperm donors have been subjected to a barrage of questions about their backgrounds. Recipients can often choose the donor who has the background, education, talents, or looks they most desire. Some recipients try to have a child who most closely resembles them; for example, if sperm donation is needed and the recipient father is Italian, tall, and artistic, the parents may look for a sperm donor with at least some of those characteristics. We've all heard about the occasional advertisement for young superstar egg donors - say an Ivy League graduate with blond hair and athletic talent.

Although views differ as to the appropriateness of these selective searches for gametes, a new question is on the horizon: Can I ask to see your genome before I pay you for your gametes? Should egg and sperm donors be entitled to genetic privacy?

Typically the detailed medical history required of egg and sperm donors includes questions about genetic abnormalities or diseases in the family. But the days when everyone knew their own health risks solely from their family history are long gone. Today there are tests available that reveal carrier gene variations that may lead to the presence of disease in an offspring if the other biological parent carries the same mutation. Other genetic variants may indicate that an individual has an increased risk of developing a range of diseases, both common and rare. 

Already, the American Society for Reproductive Medicine (ASRM) and the Society for Assisted Reproductive Technologies (SART) recommend genetic screening of donors in accordance with current guidelines on preconception testing from the American Congress of Obstetricians and Gynecologists (ACOG) and the American College of Medical Genetics and Genomics (ACMG).

In general, these recommendations for genetic screening are based on ethnicity. All donors should be tested for the presence of cystic fibrosis (CF) mutation. Donors of Asian, African, and Mediterranean descent should be screened for sickle cell trait and thalassemia. For donors of Ashkenazi Jewish background, a panel of tests includes Tay-Sachs disease, Canavan disease, familiar dysautonomia, Gaucher disease, and others.

In the general population, couples planning a traditional pregnancy are supposed to be counseled about this sort of screening before conception. When it comes to egg and sperm donors, it is much less clear how often counseling, screening, and genetic testing actually take place.

In recent years there have been news stories and anecdotal reports of children conceived with donated sperm who developed serious genetic conditions apparently inherited from the donor. The illnesses include cystic fibrosis, heart defects, spinal muscular atrophy and neurofibromatosis type 1. Particularly because sperm donors can be the biological father to multiple children, these cases cause alarm that other children - now or in the future - may be at risk.

There is no requirement for recipient parents to notify the sperm bank of genetic or other disease once a child is born. Even if they do, sperm banks may not have updated records that would allow them to contact previous recipients. Still, as a result of the recent cases, some of the larger sperm banks are working together to create a national donor gamete registry, in the hopes that information can be more easily reported and shared. This area of practice, just like preconception screening in the general population, is clearly a work in progress. More clinics and programs need to use genetics-trained professionals to counsel and educate individuals in order for screening to take place as recommended.

Beyond those few tests recommended by ASRM and ACOG, many more genetic tests are available that reveal an individual's level of risk for a myriad of diseases - risks that may be passed on to offspring. What if a prospective recipient wishes to know more about a donor's genetic makeup than the recommended screening for serious diseases? ASRM has said that additional testing may be offered by individual programs or "may be requested by the recipient couple."

Imagine a man and woman in their early 30s, trying to conceive. Because of their particular fertility issues, their reproductive endocrinologist recommends that they use donor oocytes. This couple, as it happens, know a fair amount about their own genetic makeup. The man's mother and aunt both died very young of ovarian cancer, so although he has not had specific genetic testing for the BRCA mutations which convey an elevated risk of breast and ovarian cancer, family history alone reveals that he may pass along an elevated risk.

What information is appropriate for this couple to seek from an egg donor?

Can they choose a donor based on her family history free of breast and ovarian cancer, because they want to minimize the chance of an offspring inheriting an elevated risk from both sides? Almost certainly. But should they be able to seek a donor who can produce a genetic test result that is negative for the BRCA genetic mutation? And should they be able to provide more compensation to a donor who is willing to undergo a test?

A recent set of recommendations from ASRM and SART takes the position that it is not appropriate to test gamete donors for adult onset conditions such as cancer predisposition or risk, or Huntington disease, without full consent of the donor and formal genetic counseling. These are diseases where testing the donor to get information that the recipient wants would give meaningful information about the donor's own risk of the disease, information the donor may not want to have. And the notion of providing additional compensation to a donor willing to have the genetic test that ASRM and SART say may be inappropriate raises serious questions about the notion of informed consent.

On the other hand, one reason for using an egg donor is when a woman is affected by or the carrier of a genetic disease who would prefer not to pass the disease to her offspring. Although these cases often arise when it has not been possible to identify the genetic mutation causing the disease, there may be circumstances when the prospective mother seeks an egg donor because she does not want to use pre-implantation genetic diagnosis.

Imagine a woman has lost family members to early-onset Alzheimer's disease, which has a genetic component. She is adamant she does not want to have the genetic test that would tell her whether or not she herself will get the disease. Using an egg donor would be one way to be sure that, whether or not she herself has the mutation, her child will not. But here too, while a couple may certainly scour a donor's family history for evidence of Alzheimer's disease or other forms of dementia, it is not farfetched to imagine a potential recipient who would rather "be sure" that the donor's genome does not include the mutation for the disease.

Finally, note that the norm is changing. Despite the limited number of tests recommended by ASRM and ACMG, already a number of fertility specialists are recommending that patients avail themselves of a $350 "Universal Genetic Test" marketed by Counsyl. This product includes more than 100 carrier tests. Not surprisingly, a few donor programs are requiring egg and sperm donors to have this test - and advertising it as evidence of the rigor of their screening requirements. Clearly, as genetic testing options continue to grow, so too will the demand for donors to undergo more testing and questions about appropriate testing for donors.

Susannah Baruch, JD, is a policy consultant on genetics and reproductive health in Washington, D.C.

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Created in 1999 by the Council for Responsible Genetics, the Safe Seed Pledge helps to connect non-GM seed sellers,distributors and traders to the growing market of concerned gardeners and agricultural consumers. The Pledge allows businesses and individuals to declare that they "do not knowingly buy, sell or trade genetically engineered seeds," thus assuring consumers of their commitment.
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